The brain and spinal cord are protected by a fluid called cerebrospinal fluid (CSF). CSF is produced in the brain, circulates throughout the subarchnoid space around the brain and spinal cord, and is absorbed into the sagittal sinus through a thin membrane (dura mater) that contains biological valves called arachnoid granulations (AG). When the AGs do not function properly this dynamic equilibrium is altered and the pathologic condition of hydrocephalus ensues. Hydrocephalus is an abnormal accumulation of CSF within the subarachnoid space of the brain due to impaired CSF absorption. Hydrocephalus is one of the most frequently encountered problems in Neurosurgery. 8,305 newly diagnosed cases of hydrocephalus were treated in the year 2000 and the overall cost was approximately $1.1 billion in the United States alone. The current treatment of hydrocephalus consists of implanting a shunt device that diverts the CSF from the brain into another part of the body such as the peritoneum. The shunt device consists of a one-way valve and two long tubes connected to the ventricular space and the drainage space, respectively. The treatment which was developed in the 1950's has remained essentially unchanged for over 50 years. Ventriculo-peritoneal (VP) shunts are the most common type of shunt in use but have significant shortcomings such as high failure rate (~ 50% within 2 years) and imprecise flow control resulting in under- or over-shunting. We propose an innovative approach for the treatment of hydrocephalus. The goal of our research is to develop an implantable microdevice analogous to the native biological valve that diverts excessive CSF from the subarachnoid space to the sagittal sinus. We are attempting to replace the malfunctioning arachnoid granulations that cause hydrocephalus with a miniature artificial device to restore the normal absorptive function. The proposed microfabricated arachnoid granulations (MAG) consist of an array of hollow microneedles and corresponding one-way microvalves. The microneedle array will be surgically placed to pierce the dura mater to act as a one-way outlet for CSF from the subarachnoid space to the venous sinus. Microvalves within the microneedles act as passive valves that regulate the flow of CSF to the sagittal sinus. The flow of CSF will be in response to the pressure differential between the sagittal sinus and the subarachnoid space just as in normally functioning AG. In order to achieve the goal, three specific aims are proposed: 1) Design, simulate, and fabricate MAGs capable of diverting CSF equivalent to normally functioning AG, 2) Test the MAGs in vitro using a bench-top CSF simulator, 3) Demonstrate surgical implantation and short-term functioning of the MAG using an animal model. If successful, the proposed MAG will pioneer a new era in the treatment of hydrocephalus. PUBLIC HEALTH RELEVANCE: This research project will develop an innovative implantable device for the treatment of hydrocephalus which is one of the most frequently encountered problems in Neurosurgery. An implantable microdevice that resembles the function of the native arachnoid granulations which acts as biological valves to eliminate cerebrospinal fluid will be developed using microfabrication technology. The proposed microfabricated arachnoid granulations (MAG) will make it possible to replace the malfunctioning arachnoid granulations that lead to hydrocephalus. If successful, the proposed MAG may pioneer a new era in the treatment of hydrocephalus. [unreadable] [unreadable] [unreadable]